Oral composition

ABSTRACT

An oral composition is provided which is improved in antibody stability so that the antibody may satisfactorily exert its effect after long-term storage and has a pleasant feel on use. A flavor component selected from the group consisting of carvone, anethole, cineole, methyl salicylate, eugenol, ethyl butyrate, and cinnamic aldehyde, and l-menthol are blended in a weight ratio of from 1:9 to 8:2 in an oral composition containing an antibody selected from the group consisting of a serum antibody, egg yolk antibody and milk antibody.

This is a 371 PCT/JP94/01019 filed Jun. 24, 1994.

This is a 371 PCT/JP94/01019 filed Jun. 24, 1994.

FIELD OF THE INVENTION

This invention relates to an oral composition containing an antibodywhich is effective for the prevention or treatment of dental caries andperidontal diseases and more particularly, to such an oral compositionwhich allows the antibody to exert its effect satisfactorily even afterlong-term shelf storage and presents a pleasant feel on use.

BACKGROUND OF THE INVENTION

Research has been done in the past to blend an antibody in dentifricesand other oral compositions as an active ingredient for preventingdental caries, the antibody having specific interaction withStreptococcus mutans bacterium and being effective for prohibitingadhesion of the bacterium to the dental surface and formation of dentalplaque.

Research has also been done to blend an antibody in dentifrices andother oral compositions as an active ingredient for preventingperiodontal diseases, the antibody having specific interaction withperiodontal disease associated bacteria and being effective forsuppressing colonization of the bacteria in the oral cavity.

However, there is a problem that the above-mentioned antibodies tend tobe deactivated under the influence of anionic surfactants in the oralcompositions. Thus, various studies have been made on the technique forblending antibodies in a stable manner.

Additionally the oral compositions must have a pleasant feel on usesince they are used in the oral cavity. Therefore, various flavorcomponents must be blended to improve the feel on use depending on aparticular type of consumers' favorite taste or the like although therearises a problem that many flavor components have undesirable influenceon the stability of antibodies.

Therefore, it is desired to develop an oral composition which isimproved in antibody stability and feel on use.

DISCLOSURE OF THE INVENTION

An object of the present invention is to provide an antibody-containingoral composition which is improved in antibody stability, allows theantibody to exert its effect satisfactorily even after long-term shelfstorage and presents a pleasant feel on use.

Making extensive investigations to attain the above object, theinventors have found that by using a flavor component selected from thegroup consisting of carvone, anethole, cineole, methyl salicylate,eugenol, ethyl butyrate, and cinnamic aldehyde, and l-menthol incombination in a weight ratio of from 1:9 to 8:2 in an oral compositioncontaining an antibody selected from the group consisting of a serumantibody, egg yolk antibody and milk antibody, quite unexpectedly, thereis obtained an oral composition which maintains the antibody stable andeven after long-term shelf storage, allows the antibody to retain itsactivity satisfactorily and to fully exert its effect, and provides apleasant feel on use. The present invention is predicated on thisfinding.

Therefore, the present invention provides an oral compositioncharacterized in that a flavor component selected from the groupconsisting of carvone, anethole, cineole, methyl salicylate, eugenol,ethyl butyrate, and cinnamic aldehyde, and l-menthol are blended in aweight ratio of from 1:9 to 8:2 in an oral composition containing anantibody selected from the group consisting of a serum antibody, eggyolk antibody and milk antibody.

The oral composition of the invention is prepared as dentifricesincluding toothpaste, wet toothpowder, toothpowder, and liquiddentifrice, liquid mouth refreshers such as mouthwash, solid mouthrefreshers such as troche, chewing gum, and the like. The compositioncontains an antibody selected from the group consisting of serumantibodies, egg yolk antibodies and milk antibodies as an activeingredient and further contains a flavor component selected from thegroup consisting of carvone, anethole, cineole, methyl salicylate,eugenol, ethyl butyrate, and cinnamic aldehyde, and l-menthol combinedin a weight ratio of from 1:9 to 8:2.

The antibody used herein may be any of the antibodies corresponding tovarious antigens. For example, antibodies corresponding to variousantigens of dental cariogenic bacteria may be used. There may be used anantibody against Streptococcus mutans bacterium as a dental cariogenicbacterium.

There may also be used antibodies corresponding to various antigens ofperiodontal disease associated bacteria. The periodontal diseaseassociated bacteria are ones which are generally considered as havingclose etiological relation with the periodontal diseases and include,for example, Actinobacillus actinomycetemcomitans, Porphyromonasgingivalis, Actinomyces viscosus, Prevotella intermedia, Fusobacteriumnucleatum, species of Capnocytophaga, Eikenella corrodens, Campylobacterrectus, Bacteroides forsythus, spirochetes such as of Treponemadenticola and the like.

The antibody used herein may be selected from serum antibodies or milkantibodies obtained by using antigens of the above-mentioned dentalcariogenic bacteria and periodontal disease associated bacteria in theform of whole cell, fimbriae, capsule, bacterial cell extract orbacterial surface layer polysaccharide and immunizing mammals therewith,or egg yolk antibodies obtained by immunizing fowls with the antigens.Monoclonal antibodies prepared by well-known methods are alsoacceptable.

The method of preparing the antibody, more particularly the method ofimmunizing animals, method of purifying the antibody and the like may beconventional methods. Note that illustrative examples of preparation aredescribed later as Reference Examples.

In the oral composition of the invention, either a single antibody maybe blended or two or more antibodies may be used in combination. Theamount of antibody blended is not particularly limited although the oralcomposition generally contains 0.0001 to 10% (% by weight throughout thespecification), preferably 0.002 to 5% of the antibody.

According to the invention, one or more members selected from carvone,anethole, cineole, methyl salicylate, eugenol, ethyl butyrate, andcinnamic aldehyde are blended in the antibody-containing oralcomposition, although anethole is preferably used among others.

The flavor components may be blended in isolated form although essentialoils containing a flavor component may also be blended, for example,spearmint oil in the case of carvone.

Further, l-menthol which is used along with the flavor component may beblended in isolated form although essential oils containing the same,for example, peppermint (Mentha piperita) oil and/or cornmint (Menthaarvensis) oil may also be blended.

The proportion of the flavor component and l-menthol blended is from 1:9to 8:2, preferably from 2:8 to 7:3 in weight ratio because blendingwithin this proportional range insured stable blending of the antibodyand improves feel on use by providing an appropriate combination ofrefreshingness, body and pungent taste. On the contrary, if theproportion of the flavor component blended is smaller than theabove-defined range, the body and pungent taste become short and thefeel on use deteriorates, and if the proportion of the flavor componentis larger than the above-defined range, the antibody lowers in stabilityand refreshingness becomes short, failing to achieve the object of theinvention.

Also, the amount of the flavor component blended is desirably 0.01 to0.5% of the entire composition. The feel on use will deteriorate withless than 0.01% of the flavor component whereas the antibody stabilityand feel on use will lower with more than 0.5% of the flavor component.

Further, it is desired in the present invention that the total amount ofthe flavor component and l-menthol blended be 0.1 to 5%, especially 0.3to 3% of the entire composition. The body and refreshingness becomeshort with a total blending amount of less than 0.1% whereas the pungenttaste becomes too strong with a total blending amount of more than 5%,and the antibody stability is not further improved when more amounts areblended.

In addition to the antibody, the oral composition of the invention mayhave another active ingredient blended therein, for example, enzymessuch as dextranase, amylase, protease, mutanase, lysozyme, and lyticenzyme; bactericides such as chlorhexidines, triclosan, and cetylpyridinium chloride; fluorides such as alkali metalmonofluorophosphates, sodium fluoride and stannous fluoride; as well asstannous compounds, epsilon-aminocaproic acid, tranexamic acid,allantoin, aluminum chlorohydroxyallantoin, dihydrocholesterol,glycyrrhizin salts, azulene, vitamin E, sodium chloride, andwater-soluble inorganic phosphoric acid compounds. It is especiallydesired to use alkali metal monofluorophosphates such as sodiummonofluorophosphate along with the antibody because the antibody becomesmore stable and the retentivity of the antibody after long-term shelfstorage can be kept high. In this regard, the amount of alkali metalmonofluorophosphate added is preferably 10 to 10,000 ppm calculated asfluorine. Examples of the water-soluble inorganic phosphoric acidcompound include potassium and sodium salts of orthophosphoric acid,pyrophosphoric acid, and polyphosphoric acid, with the potassium saltsof these phosphoric acids being especially preferred.

In addition to the flavor component, any other flavor components such asaliphatic alcohols having 7 to 17 carbon atoms and esters thereof,terpene hydrocarbons, phenol ethers, aldehydes, ketones and lactones andessential oils may be blended insofar as the benefits of the inventionare not adversely affected.

In the composition of the invention, any other components commonly usedmay be blended in accordance with a particular type of composition. Forexample, in the case of dentifrices, one or more of aluminum oxide,aluminum hydroxide, calcium hydrogen phosphate dihydrate or anhydride,silica gel, zirconosilicate, silicic anhydride, aluminosilicate, calciumcarbonate, calcium pyrophosphate, aluminum silicate, insoluble sodiummetaphosphate, magnesium tertiary phosphate, magnesium carbonate,calcium sulfate, and synthetic resins may be blended as an abrasivegenerally in an amount of 20 to 90% of the entire composition,especially in an amount of 20 to 60% in the case of toothpaste. It ispreferred in the invention to use silica series compounds as a mainabrasive because the antibody and dentifrice itself are further improvedin stability. The silica series compounds include precipitated silica,silica gel, aluminosilicate, and zirconosilicate with a particle size of1 to 30 μm being preferred from the aspect of use.

Further, in the dentifrice composition, carrageenan, sodiumcarboxymethyl cellulose, alkali metal alginates such as sodium alginate,gums, polyvinyl alcohol, vee gum or the like may be blended(conventional blending amount 0.3 to 5%). When an alkali metalmonofluorophosphate is blended as an active ingredient, a combined useof carrageenan and alkali metal alginate is desirable from the points ofview of stability and feel on use of the composition. Sincekappa-carrageenan (κ-carrageenan) is more effective for preventingtexture roughening of the dentifrice composition than conventionalcarrageenan (kappa and iota mixture), κ-carrageenan is the preferredcarrageenan used herein.

Furthermore, sorbitol, glycerin, propylene glycol, 1,3-butylene glycol,polyethylene glycol, xylitol, maltitol, lactitol, or the like may beblended as a humectant (conventional blending amount 10 to 70%). It ispreferred to use propylene glycol as a liquid humectant dispersion.Since the retentivity of the antibody after storage is reduced byblending a large amount of propylene glycol, it is desirable to blendsorbitol as a main humectant and use propylene glycol in admixturetherewith.

Moreover, there may be blended anionic surfactants such as sodium laurylsulfate, sodium lauroyl sarcosinate, α-olefin sulfonate, taurate, laurylmonoglyceride sulfate and lauryl monoglyceride sulfonate, and soap;nonionic surfactants such as lauroyl diethanol amide, stearylmonoglyceride, sucrose fatty acid esters, lactose fatty acid esters,lactitol fatty acid esters, maltitol fatty acid esters, andpolyoxyethylene sorbitan monostearate; ampholytic surfactants such asbetain and amino acid type surfactants (conventional blending amount 0.5to 7%); sweeteners such as saccharin sodium, stevioside, neohesperidyldihydrochalcone, taumatine, glycyrrhizin, and perillartine;preservatives such as parahydroxybenzoates and sodium benzoate; andcomponents such as gelatin and peptone.

A toothpaste may be prepared by kneading the above-mentioned componentswith an appropriate amount of water. The thus obtained toothpastecomposition is used after it is filled in appropriate containers, forexample, aluminum tubes, laminate tubes having aluminum foil laminatedwith plastic material on either surface, plastic tubes, bottles andaerosol containers.

Oral compositions other than the toothpaste may be prepared byconventional methods using a commonly used base material.

The oral composition of the invention allows the serum antibodies, eggyolk antibodies and milk antibodies to be stably retained and to fullyexert their effect over a long term, permits a choice of a flavorcomponent from a wise variety, and provides a pleasant feel on use.

Examples and Comparative Examples are given below by way of illustrationof the present invention although the present invention is not limitedto these Examples.

In the examples, all percents are by weight.

Antibody preparation process A

An antigen was first prepared by the following procedure.

(1) Preparation of PAc antigen

PAc antigen was prepared according to the method of Lehner (J. GeneralMicrobiology, 122, 217-225, 1981) by growing S. mutans 10449 in 20liters of TPY dialysis medium, centrifuging the medium, fractionatingthe resulting supernatant with 60% ammonium sulfate, and collecting theprecipitate. The precipitate was dissolved in 10 mM tris-hydrochloricacid buffer solution (pH 7.5), dialyzed with the buffer solution,adsorbed to DEAE-Sephacel column chromatograph, and eluted in accordancewith a NaCl concentration gradient. The end fraction was thenconcentrated and purified by gel filtration through Sepharose 6B.

(2) Preparation of bacterial whole cell

S. mutans 10449 was grown for 18 hours in 20 liters of TTY medium underaerobic conditions at 37° C. The culture medium was centrifuged at 8,000rpm for 20 minutes, and culture supernatant was removed. The bacteriawere collected, washed three times with phosphate buffered saline (PBS),further washed three times with sterilized distilled water, and freezedried.

(3) Preparation of bacterial cell coupled glucosyltransferase (GTF)

S. mutans 10449 was grown for 18 hours in 20 liters of TTY medium underaerobic conditions at 37° C. The culture medium was centrifuged at 8,000rpm for 20 minutes and culture supernatant was removed. The bacteriawere collected, washed three times with physiological saline, andextracted with a solution containing 4M urea and 0.5M sodium chloride atroom temperature for one hour with slow occasional stirring. Aftercentrifugation (8,000 rpm, 20 minutes), the required liquid phase wasdialyzed with 10 mM phosphate buffered saline (pH 6.0). After theprecipitate was removed by centrifugation, the supernatant was treatedwith 60% saturated ammonium sulfate, and the resulting precipitate wascollected under the above-mentioned centrifugation. The precipitate wasdissolved in the above-mentioned buffer solution and dialyzed with thebuffer solution. After the precipitate was centrifugally removed fromthe dialyzate, the supernatant was sterilized through a 0.22-μm membranefilter, obtaining an antigen for immunization.

(4) Preparation of water-soluble glucan synthetic enzyme (GTF-S)

S. mutans 10449 was grown for 18 hours in 20 liters of TTY medium underaerobic conditions at 37° C. The culture medium was centrifuged at 8,000rpm for 20 minutes, and the bacterial cell was removed. The supernatantwas treated with 55% saturated ammonium sulfate and the resultingprecipitate was centrifuged, and supernatant was discarded. Then theprecipitate was dissolved in a histidine-HCl buffer solution (pH 6.0)and dialyzed with the same buffer. The precipitate was centrifugallyremoved and the supernatant was sterilized through a 0.22-μm membranefilter and passed through a Polybuffer PBE 94 column (manufactured byPharmacia) of 2.5×25 cm. The fractions adsorbed in the column wereselectively eluted in accordance with a pH gradient using Polybuffer 74(manufactured by Pharmacia). A fraction at pH 5.5-4.9 was found to havehigh GTF activity. This fraction was collected and treated with 80%saturated ammonium sulfate, obtaining a precipitate. The precipitate wasdissolved in a 10 mM phosphate buffered saline (pH 6.0) and dialyzedwith the same buffer. The precipitate was removed by centrifugation andthe supernatant was used as an antigen.

It is to be noted that GTF activity was determined by mixing 10 μl ofsample as a substrate with 10 μl of 0.2M phosphate buffered saline (pH6.0) containing 20 mM ¹⁴ C-glucose! sucrose (0.05 ci/mol), allowingreaction to incubate for one hour, spotting the small aliquot amount ofreaction mixture on a paper filter (1×1 cm), washing it with methanol,measuring the quantity of radioactivity taken in the methanol-insolubleglucan remaining on the paper filter, and calculating GTF activitytherefrom, with the activity capable of converting 1 μmol of glucoseinto glucan within one minute per unit.

Next, a hen egg yolk antibody, serum antibody and milk antibodycorresponding to each of the above-prepared antigens were prepared bythe following methods.

(1) Preparation of hen egg yolk antibody

A W/O type emulsion was prepared by mixing 0.5 ml of a solutioncontaining 1 mg/ml of the antigen and 0.5 ml of Freund's incompleteadjuvant (FIA) in a ratio of 1:1. A hen was initially immunized byinjecting the emulsion into the left and right pectral muscles, 0.5 mleach, and successively immunized at intervals of one week, and eggs werecollected from the end of one month. While appropriate immunization wasrepeated upon detecting lowered antibody titer, eggs were collected overabout one year. To the egg yolk separated from eggs were added an equalvolume of water and further an equal volume of a 0.5% γ-carrageenansuspension. After stirring, the mixture was centrifuged at 8,000 rpm for20 minutes to provide a supernatant, which was an antibody-containingwater soluble fraction (WSF) and was measured for antibody titer beforeuse. The foregoing procedure yielded 10 ml of a liquid containing 80 to320 unit/ml (1 mg/ml) of hen egg yolk antibody.

(2) Preparation of milk antibody

The antigen was diluted to a concentration of 50 μg/ml to 200 mg/ml andmixed with an equal volume of Freund's incomplete adjuvant. Pregnantgoat, rabbit, cow and horse were immunized by subcutaneous injection ontheir back in an amount of 0.3 ml per body and thereafter immunizedthree times with the mixture of the antigen and Freund's incompleteadjuvant at intervals of 2 to 4 weeks. After parturition, the colostrumwas collected. The colostrial sample was combined with an equal volumeof 0.9% saline and centrifuged at 1,200 rpm for 60 minutes. With theupper layer of fat and the precipitate removed, the intermediate liquidcomponent was collected and adjusted to pH 4 by adding conc.hydrochloric acid. The liquid was further centrifuged at 5,000 rpm for30 minutes. After the supernatant was neutralized withtrishydroxyaminomethane, ammonium sulfate was added to the supernatantto 75% saturation, from which a precipitate was collected. Theprecipitate was dialyzed with phosphate buffered saline, obtaining amilk antibody component (endo-liquid). There was obtained a liquidcontaining 10 to 20 unit/ml (1 mg/ml) of colostrial antibody.

(3) Preparation of serum antibody

After 4 times of immunization in the same manner as described above,blood was collected, clotted and centrifuged, with the supernatant beingused as a sample. Ammonium sulfate was added to this antiserum to 50%saturation, from which a precipitate was collected, dialyzed withphosphate buffered saline, obtaining a serum antibody (endo-liquid).There was obtained a liquid containing about 80 to 320 unit/ml (1 mg/ml)of serum antibody.

Note that each of the above-prepared antibodies was measured forantibody titer by the following procedure using a bacterialagglutination test.

Antibody titer measurement

(1) Bacterial suspension

One or two colonies of S. mutans 10449 on TYC agar medium wereinoculated into 200 ml of BHI medium and anaerobically incubated at 37°C. for 18 hours. The bacteria were collected and washed three times withphysiological saline (BSA physiological saline) containing 0.1% bovineserum albumin. The bacteria as washed were suspended in BSAphysiological saline and adjusted to OD_(550nm) 1.0. The bacterialsuspension was prepared on demand.

(2) Sample antibody

Samples were prepared by diluting each antibody 20, 30, 50, 70 and 90times respectively, and then each was diluted by a factor of 2^(n).

(3) Manipulation

On a micro-plate 50 μl of the dilute antibody and 50 μm of the bacterialsuspension were mixed and agitated and thereafter allowed to stand 3hours at 37° C. and then overnight at 4° C.

(4) Detection of bacterial agglutination

On inspection of the micro-plate bottom at the end of overnight rest,agglutination was judged positive when no bacterial spots developed andnegative when even a few spots were observed.

EXAMPLES 1-9 & COMPARATIVE EXAMPLES 1-2

Toothpaste compositions of the formulation shown in Table 1 and Table 2were prepared. Immediately after preparation and after shelf storage at40° C. for one month, the antibody quantity was measured by an ELISAmethod using an immunogen, determining the antibody retentivity. Theresult is expressed as the residual activity equal to the quantity after40° C. storage divided by the quantity immediately after blending whichis 100%. The toothpaste compositions were also evaluated for feel on useby a sensory test using a special panel. The results are shown in Table1 and Table 2.

                  TABLE 1                                                         ______________________________________                                                   Com-                     Com-                                      Dentifrice para-                    para-                                     composition                                                                              tive     Example         tive                                      component  Example 1                                                                              1       2     3     Example 3                             ______________________________________                                        Anethole/l-menthol                                                                        1:20     1:9     5:5   8:2   9:1                                  Silicic anhydride                                                                         20%      20%     20%   20%   20%                                  Glycerin    30       30      30    30    20                                   Sorbitol    20       20      20    20    20                                   Sodium carboxy-                                                                           1.0      1.0     1.0   1.0   1.0                                  methyl cellulose                                                              Sodium lauryl                                                                             1.2      1.2     1.2   1.2   1.2                                  sulfate                                                                       Lauroyl     1.0      1.0     1.0   1.0   1.0                                  diethanolamide                                                                Gelatin     1.0      1.0     1.0   1.0   1.0                                  Anethole    0.05     0.1     0.5   0.4   0.45                                 l-menthol   1.0      0.9     0.5   0.1   0.05                                 Saccharin   0.1      0.1     1.0   1.0   1.0                                  Orange oil  0.05     0.05    0.05  0.05  0.05                                 Benzaldehyde                                                                              0.02     0.02    0.02  0.02  0.02                                 Sodium fluoride                                                                           0.5      0.5     0.5   0.5   0.5                                  Anti-PAc horse                                                                            0.2      0.2     0.2   0.2   0.2                                  serum antibody                                                                Water      balance  balance balance                                                                             balance                                                                             balance                               Total      100.00   100.00  100.00                                                                              100.00                                                                              100.00                                Antibody   Δ  ◯                                                                         ◯                                                                       ◯                                                                       Δ                               retentivity                                                                   (40° C./l month                                                        storage)                                                                      Feel on use                                                                              X        ◯                                                                         ◯                                                                       ◯                                                                       V                                     ______________________________________                                    

Antibody retentivity evaluation criterion

◯: retentivity 70% or more

Δ: retentivity 30% to less than 70%

×: residual quantity less than 30%

Feel on use evaluation criterion

◯: pleasant

×: monotonous flavor, unpleasant feel

V: short refreshing, unpleasant feel

                  TABLE 2                                                         ______________________________________                                        Dentifrice                                                                    composition                                                                            Example                                                              component                                                                              4       5       6     7     8     9                                  ______________________________________                                        Silicic   20%     20%     20%   20%   20%   20%                               anhydride                                                                     Glycerin  30      30      30    30    30    30                                Sorbitol  20      20      20    20    20    20                                Sodium    1.0     1.0     1.0   1.0   1.0   1.0                               carboxymethyl                                                                 cellulose                                                                     Sodium lauryl                                                                           1.2     1.2     1.2   1.2   1.2   1.2                               sulfate                                                                       Lauroyl   1.0     1.0     1.0   1.0   1.0   1.0                               diethanolamide                                                                Gelatin   1.0     1.0     1.0   1.0   1.0   1.0                               Carvone   0.4    --      --    --    --    --                                 Cineole  --       0.3    --    --    --    --                                 Methyl   --      --       0.5  --    --    --                                 salicylate                                                                    Eugenol  --      --      --     0.1  --    --                                 Ethyl butyrate                                                                         --      --      --    --     0.1  --                                 Cinnamic --      --      --    --    --     0.3                               aldehyde                                                                      l-menthol                                                                               0.5     0.5     0.5   0.5   0.5   0.5                               Saccharin                                                                               0.1     0.1     0.1   0.1   0.1   0.1                               Orange oil                                                                              0.05    0.05    0.05  0.05  0.05  0.05                              Benzaldehyde                                                                            0.02    0.02    0.02  0.02  0.02  0.02                              Sodium    0.5     0.5     0.5   0.5   0.5   0.5                               fluoride                                                                      Anti-PAc horse                                                                          0.2     0.2     0.2   0.2   0.2   0.2                               serum antibody                                                                Water    balance balance balance                                                                             balance                                                                             balance                                                                             balance                            Total    100.00  100.00  100.00                                                                              100.00                                                                              100.00                                                                              100.00                             Antibody ◯                                                                         ◯                                                                         ◯                                                                       ◯                                                                       ◯                                                                       ◯                      retentivity                                                                   (40° C./1                                                              month storage)                                                                Feel on use                                                                            ◯                                                                         ◯                                                                         ◯                                                                       ◯                                                                       ◯                                                                       ◯                      ______________________________________                                    

Antibody preparation process B

Antigens were prepared by the following processes.

(1) Preparation of Porphyromonas gingivalis whole cell antigen

Porphyromonas gingivalis 381 (FERM BP-1027) was inoculated in TODDHEWITT broth supplimented with hemin and menadione, and grown for twodays. The bacteria were collected, washed with PBS (phosphate bufferedsaline, pH 7.4) and treated with 0.5% formalin overnight, washed threetimes with PBS, and then obtained whole cell antigen.

(2) Preparation of Porphyromonas gingivalis fimbrial antigen

Porphyromonas gingivalis 381 grown for two days were collected andwashed in the same manner as above, slowly agitated for two days in PBStogether with glass beads, and passed through an injection needle (No.25) three times for separating fimbriae from the bacterial cell. Thesupernatant was separated by centrifugation at 8,000 rpm for 15 minutes,dialyzed, and freeze dried, obtaining a fimbrial antigen.

(3) Preparation of Porphyromonas gingivalis capsular antigen

The bacteria collected in the same manner as above were suspended in PBScontaining 0.01M EDTA, allowed for reaction at 60° C. for 30 minutes,and passed through an injection needle three times for separatingcapsule from the bacterial cell. Then the bacterial cell was separatedby centrifugation at 8,000 rpm for 15 minutes, and the supernatant wassubjected to ultracentrifugation at 40,000 rpm for 2 hours, obtaining asedimented residue as a capsular antigen.

(4) Preparation of Actinobacillus actinomycetemcomitans bacterialsurface layer polysaccharide antigen

Actinobacillus actinomycetemcomitans Y4 (ATCC 43718) was inoculated inTODD HEWITT broth supplimented with 1% yeast extract and grown for 3days at 37° C. in an incubator containing 5% CO₂. The bacteria werecollected, washed three times with saline, suspended in saline, andautoclaved at 121° C. for 15 minutes. After cooling, the supernatant wascollected by centrifugation at 10,000×g for 20 minutes whereupon salinewas added to the sedimented residue again and the above-mentionedextraction procedure was repeated. The combined supernatant was dialyzedextensively against distilled water and freeze dried, obtaining abacterial surface layer polysaccharide antigen.

Next, a hen egg yolk antibody, serum antibody and milk antibodycorresponding to each of the above-prepared antigens were prepared.

(1) Preparation of hen egg yolk antibody

A W/O type emulsion was prepared by mixing 0.5 ml of a solutioncontaining 1 mg/ml of the antigen and 0.5 ml of Freund's incompleteadjuvant (FIA) in a ratio of 1:1. A hen was initially immunized byinjecting the emulsion into the left and right pectral muscles, 0.5 mleach, and successively immunized at intervals of one week, and eggs werecollected from the end of one month. While appropriate immunization wasrepeated upon detecting lowered antibody titer, eggs were collected overabout one year. To the egg yolk separated from eggs were added an equalvolume of water and further an equal volume of a 0.5% γ-carrageenansuspension. After stirring, the mixture was centrifuged at 8,000 rpm for20 minutes to provide a supernatant, which was a hen egg yolk antibodysample.

(2) Preparation of serum antibody

The antigen was diluted to a concentration of 50 μg/ml to 200 mg/ml andmixed with an equal volume of Freund's incomplete adjuvant. A goat,rabbit, cow, horse and sheep were immunized by subcutaneous injection ontheir back in an amount of 0.3 ml per body and thereafter immunizedthree times with the mixture of the antigen and Freund's incompleteadjuvant at intervals of 2 to 4 weeks. Thereafter, blood was collected,clotted and centrifuged, with the supernatant being used as an antiserumsample. Ammonium sulfate was added to this antiserum to 50% saturation,from which a precipitate was collected, dialyzed against PBS, obtaininga serum antibody sample.

(3) Preparation of milk antibody

A pregnant goat, cow and sheep were subjected to 4 times of immunizationin the same manner as described above. After parturition, the colostrumwas sampled. The colostral sample was combined with an equal volume ofsaline and centrifuged at 1,200 rpm for 60 minutes. With the upper layerof fat and the precipitate removed, the intermediate liquid componentwas collected and adjusted to pH 4 by adding conc. hydrochloric acid.The liquid was further centrifuged at 5,000 rpm for 30 minutes. Afterthe supernatant was neutralized with tris(hydroxymethyl)aminomethane,ammonium sulfate was added to the supernatant to 75% saturation, fromwhich a precipitate was collected. The precipitate was dialyzed againstPBS, obtaining a milk antibody sample.

EXAMPLES 10-18 & COMPARATIVE EXAMPLES 3-4

Toothpaste compositions of the formulation shown in Tables 3 and 4 wereprepared. Immediately after preparation and after shelf storage at 40°C. for one month, the antibody quantity was measured by an ELISA methodusing an immunogen, determining the antibody retentivity. The results isexpressed as the residual activity equal to the quantity after 40° C.storage divided by the quantity immediately after blending which is100%. The toothpaste compositions were also evaluated for feel on use bya sensory test using a special panel. The results are shown in Tables 3and 4. It is to be noted that all the blending amounts (%) in theexamples are % by weight. Also note that Aa is Actinobacillusactinomycetemcomitans, Pg is Porphyromonas gingivalis, Av is Actinomycesviscosus, Pi is Prevotella intermedia, Fn is Fusobacterium nucleatum, Cris Campylobacter rectus, Bf is Bacteroides forsythus, and Td isTreponema denticola.

                  TABLE 3                                                         ______________________________________                                                   Com-                     Com-                                      Dentifrice para-                    para-                                     composition                                                                              tive     Example         tive                                      component  Example 3                                                                              10      11    12    Example 4                             ______________________________________                                        Anethole/l-menthol                                                                        1:20     1:9     5:5   8:2   9:1                                  Silicic anhydride                                                                         20%      20%     20%   20%   20%                                  Glycerin    30       30      30    30    20                                   Sorbitol    20       20      20    20    20                                   Sodium carboxy-                                                                           1.0      1.0     1.0   1.0   1.0                                  methyl cellulose                                                              Sodium lauryl                                                                             1.2      1.2     1.2   1.2   1.2                                  sulfate                                                                       Lauroyl     1.0      1.0     1.0   1.0   1.0                                  diethanolamide                                                                Gelatin     1.0      1.0     1.0   1.0   1.0                                  Anethole    0.05     0.1     0.5   0.4   0.45                                 l-menthol   1.0      0.9     0.5   0.1   0.05                                 Saccharin   0.1      0.1     1.0   1.0   1.0                                  Orange oil  0.05     0.05    0.05  0.05  0.05                                 Benzaldehyde                                                                              0.02     0.02    0.02  0.02  0.02                                 Tranexamic acid                                                                           0.05     0.05    0.05  0.05  0.05                                 Anti-Pg fimbriae                                                                          0.2      0.2     0.2   0.2   0.2                                  rabbit serum                                                                  antibody                                                                      Water      balance  balance balance                                                                             balance                                                                             balance                               Total      100.00   100.00  100.00                                                                              100.00                                                                              100.00                                Antibody   Δ  ◯                                                                         ◯                                                                       ◯                                                                       Δ                               retentivity                                                                   (40° C./l month                                                        storage)                                                                      Feel on use                                                                              X        ◯                                                                         ◯                                                                       ◯                                                                       V                                     ______________________________________                                    

Antibody retentivity evaluation criterion

◯; retentivity 70% or more

Δ: retentivity 30% to less than 70%

×: retentivity less than 30%

Feel on use evaluation criterion

◯: pleasant

×: monotonous flavor, unpleasant feel

V: short refreshing, unpleasant feel

                  TABLE 4                                                         ______________________________________                                        Dentifrice                                                                    composition                                                                            Example                                                              component                                                                              13      14      15    16    17    18                                 ______________________________________                                        Silicic   20%     20%     20%   20%   20%   20%                               anhydride                                                                     Glycerin  30      30      30    30    30    30                                Sorbitol  20      20      20    20    20    20                                Sodium    1.0     1.0     1.0   1.0   1.0   1.0                               carboxymethyl                                                                 cellulose                                                                     Sodium lauryl                                                                           1.2     1.2     1.2   1.2   1.2   1.2                               sulfate                                                                       Lauroyl   1.0     1.0     1.0   1.0   1.0   1.0                               diethanolamide                                                                Gelatin   1.0     1.0     1.0   1.0   1.0   1.0                               Carvone   0.4    --      --    --    --    --                                 Cineole  --       0.3    --    --    --    --                                 Methyl   --      --       0.5  --    --    --                                 salicylate                                                                    Eugenol  --      --      --     0.1  --    --                                 Ethyl butyrate                                                                         --      --      --    --     0.1  --                                 Cinnamic --      --      --    --    --     0.3                               aldehyde                                                                      l-menthol                                                                               0.5     0.5     0.5   0.5   0.5   0.5                               Saccharin                                                                               0.1     0.1     0.1   0.1   0.1   0.1                               Orange oil                                                                              0.05    0.05    0.05  0.05  0.05  0.05                              Benzaldehyde                                                                            0.02    0.02    0.02  0.02  0.02  0.02                              Sodium    0.05    0.05    0.05  0.05  0.05  0.05                              fluoride                                                                      Anti-Pg   0.2     0.2     0.2   0.2   0.2   0.2                               fimbriae rabbit                                                               serum antibody                                                                Water    balance balance balance                                                                             balance                                                                             balance                                                                             balance                            Total    100.00  100.00  100.00                                                                              100.00                                                                              100.00                                                                              100.00                             Antibody ◯                                                                         ◯                                                                         ◯                                                                       ◯                                                                       ◯                                                                       ◯                      retentivity                                                                   (40° C./1                                                              month storage)                                                                Feel on use                                                                            ◯                                                                         ◯                                                                         ◯                                                                       ◯                                                                       ◯                                                                       ◯                      ______________________________________                                    

    ______________________________________                                        Example 19: Dentifrice                                                        Calcium hydrogen phosphate dihydride                                                                50.0%                                                   Sorbitol              10.0                                                    Glycerin              10.0                                                    Carrageenan           1.0                                                     Sodium lauryl sulfate 1.0                                                     l-menthol             0.3                                                     Peppermint oil        0.6                                                     Eugenol               0.03                                                    Anethole              0.17                                                    Saccharin             0.1                                                     Ethanol               2.0                                                     Dextranase            0.02                                                    Anti-PAC goat milk antibody or                                                                      0.2                                                     anti-Pg surface layer                                                         polysaccharide sheep serum antibody                                           Water                 balance                                                                       100.0%                                                  Example 20: Dentifrice                                                        Silicic anhydride     30.0%                                                   Glycerin              30.0                                                    Sorbitol              20.0                                                    Carboxymethyl cellulose                                                                             1.0                                                     Sodiurn lauryl sulfate                                                                              1.2                                                     l-menthol             0.1                                                     Carvone               0.05                                                    Spearmint oil         0.4                                                     Peppermint oil        0.3                                                     Saccharin             0.1                                                     Ethanol               2.0                                                     Sodium fluoride       0.1                                                     Anti-PAC horse serum antibody or                                                                    0.1                                                     anti-Pg whole cell                                                            horse serum antibody                                                          Water                 balance                                                                       100.0%                                                  Example 21: Dentitrice                                                        Aluminum hydroxide    45.0%                                                   Sorbitol              20.0                                                    Carrageenan           0.5                                                     Carboxymethyl cellulose                                                                             1.0                                                     Lauryl diethanolamide 1.0                                                     Sucrose monolaurate   2.0                                                     l-menthol             0.6                                                     Peppermint oil        0.2                                                     Cineole               0.4                                                     Saccharin             0.1                                                     Anti-PAc cow milk antibody                                                                          0.3                                                     Water                 balance                                                                       100.0%                                                  Example 22: Dentifrice                                                        Aluminum hydroxide    45.0%                                                   Sorbitol              20.0                                                    Carrageenan           0.5                                                     Carboxymethyl cellulose                                                                             1.0                                                     Lauryl diethanolamide 1.0                                                     Sucrose monolaurate   2.0                                                     l-menthol             0.6                                                     Peppermint oil        0.2                                                     Cineole               0.4                                                     Saccharin             0.1                                                     Anti-Pg fimbriae horse serum antibody                                                               0.2                                                     Anti-Aa fimbriae horse serum antibody                                                               0.2                                                     Water                 balance                                                                       100.0%                                                  Example 23: Dentifrice                                                        Calcium hydrogen phosphate                                                                          45.0%                                                   Carboxymethyl cellulose                                                                             1.0                                                     Carrageenan           0.5                                                     Sorbitol              35.0                                                    Propylene glycol      3.0                                                     Sodium N-lauroylmethyltaurine                                                                       0.5                                                     Gelatin               1.0                                                     Ethyl p-hydroxybenzoate                                                                             0.2                                                     Saccharin sodium      0.1                                                     l-menthol             0.6                                                     Methyl salicylate     0.3                                                     Sodium monofluorophosphate                                                                          0.7                                                     Anti-PAC hen egg antibody or                                                                        0.4                                                     anti-Av fimbriae egg antibody                                                 Water                 balance                                                                       100.0%                                                  Example 24: Dentifrice                                                        Aluminum hydroxide    40.0%                                                   Sodium carboxymethyl cellulose                                                                      1.0                                                     Carrageenan           0.5                                                     Sorbitol              35.0                                                    Propylene glycol      3.0                                                     Sodium N-myristoylmethyltaurine                                                                     0.5                                                     Peptide               1.0                                                     Methyl p-hydroxybenzoate                                                                            0.2                                                     Saccharin sodium      0.1                                                     l-menthol             0.5                                                     Peppermint oil        0.2                                                     Cinnamic aldehyde     0.15                                                    Spice mix flavor      0.05                                                    Anti-PAC sheep serum antibody or                                                                    0.5                                                     anti-Pi surface layer of                                                      polysaccharide sheep serum antibody                                           Water                 balance                                                                       100.0%                                                  Example 25: Dentifrice                                                        Silicic anhydride     20.0%                                                   Sodium carboxymethyl cellulose                                                                      1.0                                                     Sorbitol              50.0                                                    Polyethylene glycol   5.0                                                     Sodium N-palmitoylmethyltaurine                                                                     0.5                                                     Casein                1.0                                                     Sodium p-hydroxybenzoate                                                                            0.2                                                     Saccharin sodium      0.1                                                     l-menthol             0.3                                                     Cineole               0.1                                                     Ethyl butyrate        0.01                                                    Sodium fluoride       0.2                                                     Anti-GTF hen egg antibody                                                                           0.3                                                     Water                 balance                                                                       100.0%                                                  Example 26: Dentifrice                                                        Silicic anhydride     20.0%                                                   Sodium carboxymethyl cellulose                                                                      1.0                                                     Sorbitol              50.0                                                    Polyethylene glycol   5.0                                                     Sodium N-palmitoylmethyltaurine                                                                     0.5                                                     Casein                1.0                                                     Sodium p-hydroxybenzoate                                                                            0.2                                                     Saccharin sodium      0.1                                                     l-menthol             0.3                                                     Cineole               0.1                                                     Ethyl butyrate        0.01                                                    Tranexamic acid       0.1                                                     Anti-Fn whole cell    0.3                                                     hen egg antibody                                                              Water                 balance                                                                       100.0%                                                  Example 27: Mouthwash                                                         Ethanol               20.0%                                                   l-menthol             0.2                                                     Peppermint oil        0.2                                                     Eugenol               0.1                                                     Cineole               0 05                                                    Anethole              0.03                                                    Saccharin             0.05                                                    Lauryl diethanolamide 0.3                                                     Chlorohexidine gluconate                                                                            0.01                                                    Anti-GTF horse serum antibody or                                                                    0.1                                                     anti-Cr surface layer                                                         polysaccharide goat serum antibody                                            Water                 balance                                                                       100.0%                                                  Example 28: Mouthwash                                                         Sorbitol              10.0%                                                   Ethanol               20.0                                                    Sodium N-myristoyltaurine                                                                           0.5                                                     Sucrose stearate      1.0                                                     Peptide               0.5                                                     Methyl p-hydroxybenzoate                                                                            0.1                                                     Stevioside            0.1                                                     l-menthol             0.2                                                     Methyl salicylate     0.3                                                     Cinnamic aldehyde     0.1                                                     Ethyl butyrate        0.05                                                    Dextranase            0.2                                                     Sodium fluoride       0.2                                                     Anti-Aa surface layer polysaccharide                                                                0.2                                                     hen egg antibody                                                              Water                 balance                                                                       100.0%                                                  Example 29: Mouthwash                                                         Sorbitol              10.0%                                                   Ethanol               20.0                                                    Sodium N-myristoyltaurine                                                                           0.5                                                     Sucrose stearate      1.0                                                     Peptide               0.5                                                     Methyl p-hydroxybenzoate                                                                            0.1                                                     Stevioside            0.1                                                     l-menthol             0.2                                                     Methyl salicylate     0.3                                                     Cinnamic aldehyde     0.1                                                     Ethyl butyrate        0.05                                                    Dextranase            0.2                                                     Cetyl pyridinium chloride                                                                           0.05                                                    Anti-Bf whole cell    0.2                                                     hen egg antibody                                                              Water                 balance                                                                       100.0%                                                  Example 30: Mouthwash                                                         Sorbitol              10.0%                                                   Ethanol               20.0                                                    Sodium N-stearoylmethyltaurine                                                                      0.5                                                     POE (20) sorbitan monooleate                                                                        1.0                                                     Collagen              0.5                                                     Methyl p-hydroxybenzoate                                                                            0.1                                                     Saccharin sodium      0.1                                                     l-menthol             0.05                                                    Carvone               0.1                                                     Spearmint oil         0.3                                                     Peppermint oil        0.3                                                     Anti-PAC cow milk antibody or                                                                       0.4                                                     anti-Td surface layer                                                         polysaccharide cow milk antibody                                              Water                 balance                                                                       100.0%                                                  Example 31: Tablet                                                            Gum arabic            6.0%                                                    Glucose               72.0                                                    Gelatin               3.0                                                     l-menthol             0.2                                                     Cineole               0.1                                                     Benzaldehyde          0.05                                                    Sodium ascorbate      0.1                                                     Anti-PAc goat milk antibody or                                                                      0.1                                                     anti-Aa capsule goat milk antibody                                            Water                 balance                                                                       100.0%                                                  Example 32: Chewing gum                                                       Gum base              43.9%                                                   Calcium carbonate     2.0                                                     Hydrolyzed starch     15.0                                                    Sugar                 29.0                                                    Sucrose palmitate     1.0                                                     Fructose              4.0                                                     Aldose                3.0                                                     l-menthol             0.6                                                     Carvone               0.4                                                     Fruit mix flavor      1.0                                                     Anti-PAc hen egg antibody or                                                                        0.1                                                     anti-Pg fimbriae hen egg antibody                                             Water                 balance                                                                       100.0%                                                  ______________________________________                                    

We claim:
 1. An oral composition characterized in that a flavorcomponent selected from the group consisting of cineole, methylsalicylate, ethyl butyrate, and cinnamic aldehyde, and l-menthol areblended in a weight ratio of from 1:9 to 8:2 in an oral compositioncontaining an antibody selected from the group consisting of a serumantibody, egg yolk antibody and milk antibody.
 2. The oral compositionof claim 1 wherein said antibody is an antibody specific for dentalcariogenic bacteria.
 3. The oral composition of claim 2 wherein saidcariogenic bacteria is Streptococcus mutans.
 4. The oral composition ofclaim 1 wherein said antibody is an antibody specific for periodontaldisease associated bacteria.
 5. The oral composition of claim 4 whereinsaid periodontal disease associated bacteria is selected from the groupconsisting of Actinobacillus actinomycetemcomitans, Porphyromonasgingivalis, Actinomyces viscosus, Prevotella intermedia, Fusobacteriumnucleatum, species of Capnocytophaga, Campylobacter rectus, Bacteroidesforsythus, and Spirochaeta such as Treponema denticola.
 6. An oralcomposition according to claim 1, wherein the flavor component and thel-menthol are blended in a weight ratio of from 2:8 to 7:3.
 7. An oralcomposition according to claim 1, wherein the flavor component iscineole.
 8. An oral composition according to claim 1, wherein the flavorcomponent is methyl salicylate.
 9. An oral composition according toclaim 1, wherein the flavor component is ethyl butyrate.
 10. An oralcomposition according to claim 1, wherein the flavor component iscinnamic aldehyde.